TTLL9
protein-codingtubulin tyrosine ligase like 9, the group of Tubulin tyrosine ligase family
Gene summary
Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization. Predicted to act upstream of or within protein polyglutamylation. Predicted to be located in microtubule. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Jun 2026]
- C20orf125
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~74.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0018393
Submitter: King Faisal Specialist Hospital and Research Center
Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Moderate with total score of 8. Single variant segregation (3 points), experimental evidence: Animal model (4 points) and testicular expression (1 points) (PMID: 27257088).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TTLL9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001008409.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 76 | 76 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 78 | 1 | 0 | 79 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001008409.1 | 14 | MANE Select | |
| Ensembl | ENSP00000442515.1 | 14 | MANE Select | |
| RefSeq | NP_001354549.1 | 12 | Standard | |
| Ensembl | ENSP00000308980.5 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Carboxyterminal post-translational modifications of tubulin
Biological Process
- cellular protein modification process
Molecular Function
- ATP binding
- ligase activity
Cellular Component
- cytoplasm
- microtubule
- cilium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375938
- Coding exons
- 14
- Length
- 74260
- Individuals with no LoFs
- 124656
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 155
- Defined
- 124811
- p
- 0.000621
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.436 | 250 | 270 | 0.925 | 0.0000166 | 2905 |
| Missense (PolyPhen) | 88 | 101.8 | 0.86444 | 1072 | ||
| Synonymous | 1.21 | 85 | 100 | 0.846 | 0.00000617 | 789 |
| Loss of Function | 0.318 | 28 | 29.9 | 0.937 | 0.00000153 | 326 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00052 | 0.00045 | rare |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00061 | 0.00061 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00060 | 0.00060 | rare |
| South Asian | 0.00059 | 0.00059 | rare |
| Other | 0.0017 | 0.0016 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable tubulin polyglutamylase that forms polyglutamate side chains on tubulin. Probably acts when complexed with other proteins (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.820
- RVIS EVS
- 0.42
- RVIS percentile EVS
- 77.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.206
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |